MCID: ABL002
MIFTS: 54

Ablepharon-Macrostomia Syndrome

Categories: Genetic diseases, Rare diseases, Eye diseases, Fetal diseases, Skin diseases

Aliases & Classifications for Ablepharon-Macrostomia Syndrome

MalaCards integrated aliases for Ablepharon-Macrostomia Syndrome:

Name: Ablepharon-Macrostomia Syndrome 57 75 37 40 73
Ablepharon Macrostomia Syndrome 12 76 53 59 29 6 44 15
Ams 57 53 75
Eye Abnormalities 44 73
Congenital Ablepharon, Absent Eyelashes/eyebrows, Macrostomia, Auricular, Nasal, Genital and Other Systemic Anomalies 53
Poikiloderma with Neutropenia, Clericuzio Type 12
Macrostomia 44

Characteristics:

Orphanet epidemiological data:

59
ablepharon macrostomia syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
overlapping features with barber-say syndrome


HPO:

32
ablepharon-macrostomia syndrome:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Ablepharon-Macrostomia Syndrome

NIH Rare Diseases : 53 Ablepharon macrostomia syndrome is genetic disorder characterized by absent eyelids (ablepharon) and very large mouth (macrostomia). Other common signs and symptoms include abnormal external ears, fusion (syndactyly) of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations, and developmental delay. Other reported findings include underdeveloped cheeks (malar hypoplasia), absent or very small (hypoplastic) nipples, umbilical abnormalities and growth retardation. It belongs to a group of diseases called ectodermal dysplasias (genetic disorders that involve defects in the skin, hair, nails, sweat glands, and/or teeth). Ablepharon macrostomia syndrome is caused by mutations in the TWIST2 gene. Inheritance is autosomal dominant, but most cases are sporadic (when there are no other cases in the family). Treatment is aimed toward correcting the problems that are present. Mutations in TWIST2 gene also cause the Barber Say syndrome and Setleis syndrome, other ectodermal dysplasia syndromes which have very similar features.  

MalaCards based summary : Ablepharon-Macrostomia Syndrome, also known as ablepharon macrostomia syndrome, is related to walker-warburg syndrome and barber-say syndrome, and has symptoms including eye manifestations and dry skin. An important gene associated with Ablepharon-Macrostomia Syndrome is TWIST2 (Twist Family BHLH Transcription Factor 2), and among its related pathways/superpathways are Ectoderm Differentiation and Signaling pathways regulating pluripotency of stem cells. Affiliated tissues include skin, eye and bone, and related phenotypes are hearing impairment and global developmental delay

OMIM : 57 Ablepharon-macrostomia syndrome is a congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth (summary by Marchegiani et al., 2015). (200110)

UniProtKB/Swiss-Prot : 75 Ablepharon-macrostomia syndrome: A congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth.

Disease Ontology : 12 A syndrome characterized by by the association of ablepharon, macrostomia, abnormal external ears, syndactyly of the hands and feet, skin findings (such as dry and coarse skin or redundant folds of skin), absent or sparse hair, genital malformations and developmental delay. Other reported manifestations include malar hypoplasia, absent or hypoplastic nipples, umbilical abnormalities and growth retardation. It is that has material basis in heterozygous mutation in the TWIST2 gene on chromosome 2q37.

Wikipedia : 76 Ablepharon macrostomia syndrome (AMS) is an extremely rare autosomal recessive genetic disorder... more...

Related Diseases for Ablepharon-Macrostomia Syndrome

Diseases related to Ablepharon-Macrostomia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 190)
# Related Disease Score Top Affiliating Genes
1 walker-warburg syndrome 31.3 FKRP FKTN LARGE1 POMGNT1 POMT1
2 barber-say syndrome 30.5 CYP26C1 LAX1 TWIST2
3 muscular dystrophy 29.0 FKRP FKTN LARGE1 POMGNT1 POMT1
4 macrostomia, isolated 12.4
5 mandibulofacial dysostosis with macroblepharon and macrostomia 12.2
6 poikiloderma with neutropenia 12.1
7 dwarfism, mental retardation, and eye abnormality 12.0
8 apparent mineralocorticoid excess 11.9
9 phace syndrome 11.6
10 acute mountain sickness 11.2
11 walker dyson syndrome 11.2
12 alport syndrome, x-linked 11.1
13 dysplastic nevus syndrome 10.9
14 hemosiderosis 10.9
15 frontonasal dysplasia 1 10.8
16 microphthalmia 10.8
17 fryns microphthalmia syndrome 10.5 PAX6 SOX2
18 congenital muscular dystrophy with intellectual disability 10.5 FKRP LARGE1 POMT1
19 focal facial dermal dysplasia 10.5 CYP26C1 TWIST2
20 congenital muscular dystrophy with cerebellar involvement 10.5 FKRP POMGNT1 POMT1
21 congenital muscular dystrophy without intellectual disability 10.5 FKRP FKTN POMT1
22 muscular dystrophy, congenital, 1b 10.5 FKRP FKTN
23 muscular dystrophy-dystroglycanopathy 10.4 FKRP POMGNT1 POMT1
24 muscular dystrophy, limb-girdle, type 2l 10.4 FKRP FKTN POMT1
25 muscular dystrophy-dystroglycanopathy , type c, 4 10.4 FKRP FKTN
26 congenital nervous system abnormality 10.4 FKTN POMGNT1 POMT1
27 say syndrome 10.4
28 renal hypodysplasia/aplasia 3 10.3 FRAS1 FREM2
29 muscular dystrophy-dystroglycanopathy , type a, 1 10.2 FKRP FKTN LARGE1 POMT1
30 cutis laxa 10.2
31 congenital aphakia 10.2 PAX6 SOX2
32 muscular dystrophy-dystroglycanopathy , type b, 5 10.2 FKRP FKTN POMGNT1 POMT1
33 neutropenia 10.2
34 muscular dystrophy, congenital, lmna-related 10.2 FKRP FKTN POMGNT1 POMT1
35 limb-girdle muscular dystrophy 10.1 FKRP FKTN POMGNT1 POMT1
36 ectropion 10.1 PAX6 TWIST2
37 cryptophthalmos 10.0 FRAS1 FREM2
38 prostatitis 10.0
39 muscular dystrophy-dystroglycanopathy , type b, 6 10.0 FKRP FKTN LARGE1 POMGNT1 POMT1
40 muscular dystrophy-dystroglycanopathy , type a, 4 9.9 FKRP FKTN LARGE1 POMGNT1 POMT1
41 muscle eye brain disease 9.9 FKRP FKTN LARGE1 POMGNT1 POMT1
42 leukemia 9.9
43 aging 9.9
44 cataract 9.8
45 thyroiditis 9.8
46 dwarfism 9.8
47 endotheliitis 9.8
48 arteries, anomalies of 9.7
49 prader-willi syndrome 9.7
50 prostate cancer 9.7

Graphical network of the top 20 diseases related to Ablepharon-Macrostomia Syndrome:



Diseases related to Ablepharon-Macrostomia Syndrome

Symptoms & Phenotypes for Ablepharon-Macrostomia Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
cryptophthalmos
ablepharon (absent eyelids)
microblepharon
eyebrows absent
more
Genitourinary External Genitalia Male:
ambiguous genitalia

Head And Neck Mouth:
macrostomia
short upper lip (in some patients)
bilateral deficiency of lateral lower lip (in some patients)
unfused labial commissures (in some patients)
absent gingiva (in some patients)

Head And Neck Ears:
external ears rudimentary

Chest Breasts:
nipples absent or rudimentary

Skeletal Hands:
syndactyly of fingers, variable (in some patients)
shortening of metacarpals, variable (in some patients)
fifth-finger camptodactyly (in some patients)

Skin Nails Hair Hair:
lanugo absent

Skin Nails Hair Skin:
dry skin
coarse skin
redundant folds

Genitourinary External Genitalia Female:
ambiguous genitalia

Head And Neck Face:
zygomatic arches absent

Head And Neck Nose:
shape abnormal
deficiency of lateral alae nasi (in some patient)

Abdomen External Features:
ventral hernia

Skeletal Feet:
syndactyly of toes, variable (in some patients)
clubfeet (in some patients)

Neurologic Central Nervous System:
language delayed


Clinical features from OMIM:

200110

Human phenotypes related to Ablepharon-Macrostomia Syndrome:

59 32 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000365
2 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
3 depressed nasal bridge 59 32 occasional (7.5%) Occasional (29-5%) HP:0005280
4 corneal opacity 59 32 frequent (33%) Frequent (79-30%) HP:0007957
5 delayed speech and language development 59 32 hallmark (90%) Very frequent (99-80%) HP:0000750
6 umbilical hernia 59 32 frequent (33%) Frequent (79-30%) HP:0001537
7 microtia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008551
8 anteverted nares 59 32 frequent (33%) Frequent (79-30%) HP:0000463
9 visual impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000505
10 thin skin 59 32 frequent (33%) Frequent (79-30%) HP:0000963
11 corneal erosion 59 32 occasional (7.5%) Occasional (29-5%) HP:0200020
12 microdontia 59 32 frequent (33%) Frequent (79-30%) HP:0000691
13 dry skin 59 32 frequent (33%) Frequent (79-30%) HP:0000958
14 growth delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001510
15 aplasia/hypoplasia of the nipples 59 32 frequent (33%) Frequent (79-30%) HP:0006709
16 myopia 59 32 frequent (33%) Frequent (79-30%) HP:0000545
17 underdeveloped nasal alae 59 32 hallmark (90%) Very frequent (99-80%) HP:0000430
18 wide mouth 59 32 hallmark (90%) Very frequent (99-80%) HP:0000154
19 hypoplasia of the maxilla 59 32 frequent (33%) Frequent (79-30%) HP:0000327
20 fine hair 59 32 hallmark (90%) Very frequent (99-80%) HP:0002213
21 hypoplasia of penis 59 32 frequent (33%) Frequent (79-30%) HP:0008736
22 abnormal hair pattern 59 32 occasional (7.5%) Occasional (29-5%) HP:0010720
23 redundant skin 59 32 hallmark (90%) Very frequent (99-80%) HP:0001582
24 thin vermilion border 59 32 occasional (7.5%) Occasional (29-5%) HP:0000233
25 ambiguous genitalia 59 32 frequent (33%) Frequent (79-30%) HP:0000062
26 abnormality of skin pigmentation 59 32 occasional (7.5%) Occasional (29-5%) HP:0001000
27 camptodactyly of finger 59 32 frequent (33%) Frequent (79-30%) HP:0100490
28 toe syndactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001770
29 atresia of the external auditory canal 59 32 occasional (7.5%) Occasional (29-5%) HP:0000413
30 sparse hair 59 32 hallmark (90%) Very frequent (99-80%) HP:0008070
31 omphalocele 59 32 occasional (7.5%) Occasional (29-5%) HP:0001539
32 absent eyelashes 59 32 hallmark (90%) Very frequent (99-80%) HP:0000561
33 abnormality of female external genitalia 59 32 frequent (33%) Frequent (79-30%) HP:0000055
34 excessive wrinkled skin 59 32 frequent (33%) Frequent (79-30%) HP:0007392
35 breast hypoplasia 59 32 frequent (33%) Frequent (79-30%) HP:0003187
36 cryptophthalmos 59 32 frequent (33%) Frequent (79-30%) HP:0001126
37 absent eyebrow 59 32 hallmark (90%) Very frequent (99-80%) HP:0002223
38 ablepharon 59 32 hallmark (90%) Very frequent (99-80%) HP:0011224
39 hypertelorism 32 HP:0000316
40 abnormal nasal morphology 32 HP:0005105
41 abnormality of the mouth 32 HP:0000153
42 talipes equinovarus 32 occasional (7.5%) HP:0001762
43 cheekbone underdevelopment 59 Very frequent (99-80%)
44 short metacarpal 32 occasional (7.5%) HP:0010049
45 microtia, third degree 32 HP:0011267
46 short upper lip 32 occasional (7.5%) HP:0000188
47 ventral hernia 32 HP:0002933
48 hypoplasia of the zygomatic bone 32 hallmark (90%) HP:0010669

UMLS symptoms related to Ablepharon-Macrostomia Syndrome:


eye manifestations, dry skin

MGI Mouse Phenotypes related to Ablepharon-Macrostomia Syndrome:

46 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.21 SOX2 TWIST2 CYP26C1 FKRP FKTN FRAS1
2 craniofacial MP:0005382 10.19 CYP26C1 FKRP FRAS1 FREM2 LARGE1 PAX6
3 cardiovascular system MP:0005385 10.16 FKRP FRAS1 FREM2 LARGE1 PAX6 POMGNT1
4 mortality/aging MP:0010768 10.13 CYP26C1 FKRP FKTN FRAS1 FREM2 LARGE1
5 immune system MP:0005387 10.07 CPN1 FKRP FKTN LARGE1 LAX1 PAX6
6 digestive/alimentary MP:0005381 10.02 PAX6 POMGNT1 SMAD4 SOX2 TWIST2 FRAS1
7 embryo MP:0005380 10 CYP26C1 FKTN FREM2 PAX6 POMT1 SMAD4
8 muscle MP:0005369 9.96 FKRP FKTN FREM2 LARGE1 PAX6 POMGNT1
9 hearing/vestibular/ear MP:0005377 9.8 FREM2 LARGE1 PAX6 SOX2 TWIST2
10 reproductive system MP:0005389 9.76 FREM2 LARGE1 OCRL PAX6 POMGNT1 SMAD4
11 skeleton MP:0005390 9.56 FKRP FRAS1 FREM2 LARGE1 PAX6 SMAD4
12 vision/eye MP:0005391 9.28 LARGE1 OCRL PAX6 POMGNT1 SOX2 TWIST2

Drugs & Therapeutics for Ablepharon-Macrostomia Syndrome

Search Clinical Trials , NIH Clinical Center for Ablepharon-Macrostomia Syndrome

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Cochrane evidence based reviews: eye abnormalities

Genetic Tests for Ablepharon-Macrostomia Syndrome

Genetic tests related to Ablepharon-Macrostomia Syndrome:

# Genetic test Affiliating Genes
1 Ablepharon Macrostomia Syndrome 29 TWIST2

Anatomical Context for Ablepharon-Macrostomia Syndrome

MalaCards organs/tissues related to Ablepharon-Macrostomia Syndrome:

41
Skin, Eye, Bone, Breast

Publications for Ablepharon-Macrostomia Syndrome

Articles related to Ablepharon-Macrostomia Syndrome:

(show all 19)
# Title Authors Year
1
Use of the Masquerade Flap in Ablepharon-Macrostomia Syndrome: A Case Report. ( 29538102 )
2018
2
Barber-Say Syndrome and Ablepharon-Macrostomia Syndrome: A Patient's View. ( 28690482 )
2017
3
Barber-Say syndrome and Ablepharon-Macrostomia syndrome: An overview. ( 27196381 )
2016
4
A Case Report of Ablepharon-Macrostomia Syndrome with Amniotic Membrane Grafting. ( 26600791 )
2015
5
Ablepharon macrostomia syndrome: A distinct genetic entity clinically related to the group of FRAS-FREM complex disorders. ( 24115501 )
2013
6
Clinical variant of ablepharon macrostomia syndrome. ( 23198177 )
2011
7
Ablepharon-Macrostomia syndrome--extension of the phenotype. ( 22002929 )
2011
8
Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome. ( 21595001 )
2011
9
Case report supporting that the Barber-Say and ablepharon macrostomia syndromes could represent one disorder. ( 19760652 )
2009
10
Ablepharon-macrostomia syndrome in a 46-year-old woman. ( 15103726 )
2004
11
Ablepharon-macrostomia syndrome. ( 11807864 )
2002
12
Intermediate form of ablepharon-macrostomia syndrome with CNS abnormalities. ( 11746001 )
2001
13
Familial occurrence of ablepharon macrostomia syndrome: eyelid structure and surgical considerations. ( 10721975 )
2000
14
Ablepharon-macrostomia syndrome: first report of familial occurrence. ( 11038439 )
2000
15
Ablepharon macrostomia syndrome with associated cutis laxa: possible localization to 18q. ( 8834257 )
1996
16
Congenital shortening of the anterior lamella of all eyelids: the so-called ablepharon macrostomia syndrome. ( 8746822 )
1995
17
Ablepharon macrostomia syndrome. ( 2036354 )
1991
18
A new feature of the ablepharon macrostomia syndrome: zygomatic arch absence. ( 3293678 )
1988
19
Ablepharon macrostomia syndrome. ( 4003491 )
1985

Variations for Ablepharon-Macrostomia Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Ablepharon-Macrostomia Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 TWIST2 p.Glu75Lys VAR_074675 rs796065049

ClinVar genetic disease variations for Ablepharon-Macrostomia Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TWIST2 NM_057179.2(TWIST2): c.223G> A (p.Glu75Lys) single nucleotide variant Pathogenic rs796065049 GRCh38 Chromosome 2, 238848438: 238848438
2 TWIST2 NM_057179.2(TWIST2): c.223G> A (p.Glu75Lys) single nucleotide variant Pathogenic rs796065049 GRCh37 Chromosome 2, 239757079: 239757079

Expression for Ablepharon-Macrostomia Syndrome

Search GEO for disease gene expression data for Ablepharon-Macrostomia Syndrome.

Pathways for Ablepharon-Macrostomia Syndrome

Pathways related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.49 PAX6 SMAD4 SOX2
2 11.27 PAX6 SMAD4 SOX2
3 10.38 FKRP FKTN LARGE1 POMGNT1 POMT1

GO Terms for Ablepharon-Macrostomia Syndrome

Cellular components related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.17 CPN1 FKRP FKTN LARGE1 LAX1 OCRL

Biological processes related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anterior/posterior pattern specification GO:0009952 9.54 CYP26C1 PAX6 SMAD4
2 pituitary gland development GO:0021983 9.46 PAX6 SOX2
3 neuron fate commitment GO:0048663 9.43 PAX6 SMAD4
4 protein O-linked glycosylation GO:0006493 9.43 LARGE1 POMGNT1 POMT1
5 morphogenesis of an epithelium GO:0002009 9.4 FRAS1 FREM2
6 protein glycosylation GO:0006486 9.35 FKRP FKTN LARGE1 POMGNT1 POMT1
7 eye development GO:0001654 9.33 FREM2 PAX6 SOX2
8 glycoprotein biosynthetic process GO:0009101 9.32 FKRP LARGE1
9 protein O-linked mannosylation GO:0035269 8.92 FKRP FKTN LARGE1 POMT1

Molecular functions related to Ablepharon-Macrostomia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 R-SMAD binding GO:0070412 8.62 PAX6 SMAD4

Sources for Ablepharon-Macrostomia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
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44 MeSH
45 MESH via Orphanet
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49 NCI
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51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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